The complete human c-abl oncogene has been isolated from a cosmid library. By analysis of a series of mouse-human somatic cell hybrids using a c-abl-specific probe, human c-abl could be assigned to chromosome 9. Subsequently, it was demonstrated that in chronic myelogenous leukemia (CML) c-abl is translocated from chromosome 9 to 22, the Philadelphia chromosome (Ph1). This finding argues for a possible involvement of c-abl in CML and demonstrates, for the first time, that this translocation is reciprocal. Using a similar approach, the translocation of c-sis from chromosome 22 to 9 could be demonstrated in the Philadelphia chromosome. Sequences encoding the tyrosine phosphorylation acceptor region of the human c-abl oncogene have been identified and their nucleic acid sequences determined. An extensive sequence homology between this region of c-abl and the acceptor regions of the v-src, v-yes and v-fes family of viral oncogenes was shown to exist. These findings argue that these different oncogenes with tyrosine protein kinase activity were probably derived from a common progenitor and may represent members of a diverse family of cellular protein kinases.